Soft tissue-optimised micro-computed tomographic imaging for the study of early stages of colorectal cancer.

Abstract

Colorectal cancer (CRC) is the third most common cause of cancer-related deaths worldwide, where diagnosis at early stage is vital for effective treatment. We hypothesise that high-resolution 3D imaging can reveal aspects of CRC initiation and progression that are not easily perceived through 2D histology, the current gold standard for diagnosis. We employed soft tissue-optimised X-ray micro-computed tomography (µCT) to explore how the colonic structure changes during early stages of CRC. Azoxymethane and dextran sodium sulphate (AOM/DSS) were used to induce inflammation-associated CRC in 36 male C57BL/6J mice, recreating the conditions of three distinct stages of CRC: early-initiation, mid-progression and late-cancerous tumours. To increase the inherently low X-ray contrast of the colon, so-called in-line phase contrast synchrotron µCT imaging was employed. This advanced imaging technique provides increased image contrast of soft tissues, due to the coherence of the synchrotron source. Our sample preparation protocol for µCT imaging involved fixation in 10% neutral buffered formaldehyde for 24 hours and embedding in cylindrical wax blocks (5 mm diameter and height). Formalin-fixed paraffin-embedded colons of 18 controls and 18 CRC-treated mice were scanned at the I13-2 beamline of Diamond Light Source, the UK’s national synchrotron. The high spatial resolution (pixel-size was 2.2 µm), the high image contrast and the 3D results allowed for resolving the microstructural details of colonic crypts, which play a significant role in identifying changes of colonic structures during different stages of CRC. We are currently studying and identifying structural markers of early-stage CRC, with the aim to investigate how the novel high-resolution 3D µCT data can complement and improve the diagnostic information from microscopic images of conventional 2D histology slides. In the long run, our ambition is to establish the foundations for routine ‘3D X-ray histology’ using lab-based µCT for the diagnosis of soft tissue-related diseases such as CRC.

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Identifiers

ORCID for Harry Rossides: orcid.org/0000-0002-7547-0256

ORCID for Sylvia Pender: orcid.org/0000-0001-6332-0333

ORCID for Philipp Schneider: orcid.org/0000-0001-7499-3576

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